OBJECTIVE: This study aims to discover short-length anticancer peptides derived from pardaxin 6 through an in silico approach.
METHODS: Fragmented peptides ranging from 5 to 15 amino acids were derived from the pardaxin 6 parental peptide. These peptides were further replaced with one residue and, along with the original fragmented peptides, were predicted for their SVM scores and physicochemical properties. The top 5 derivative peptides were further examined for their toxicity, hemolytic probability, peptide structures, docking models, and energy scores using various web servers. The trend of in silico analysis outputs across 5 to 15 amino acid fragments was further analyzed.
RESULTS: Results showed that when the amino acids were increased, SVM scores of the original fragmented peptides were also increased. Designed peptides had increased SVM scores, which was aligned with previous studies where the single residue replacement transformed the non-anticancer peptide into an anticancer agent. Moreover, in vitro studies validated that the designed peptides retained or enhanced anticancer effects against different cancer cell lines. Interestingly, a decreasing trend was observed in those fragmented derivative peptides.
CONCLUSION: Single residue replacement in fragmented pardaxin 6 was found to produce stronger anticancer agents through in silico predictions. Through bioinformatics tools, fragmented peptides improved the efficiency of marine-derived drugs with higher efficacy and lower hemolytic effects in treating cancers.
PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion.
RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy.
CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.
METHODS: The study involved conducting intradermal injections on four cadavers and participants using a 2 mm length, 34-gauge needle (N-Finders, Inc., South Korea). During the cadaveric study, the polynucleotide prefilled syringe was dyed green, and an anatomist performed dissections, removing only the skin layer. Ultrasonographic observations were carried out to ensure accurate intradermal injection placement.
RESULTS: In all four cadavers, the facial injections at the anterior cheek region were precisely administered intradermally at a 30-degree injection angle. However, the 90-degree injection was found just below the dermal layer upon skin layer removal.
DISCUSSION: The findings suggest that using a 2 mm needle length allows for easy and convenient intradermal injections.
METHODS: This is an 18-month cluster-randomized, open-label, parallel-arm controlled trial conducted at 14 public hospitals in the Perak state of Malaysia. Patients aged 60 and above, who have at least one medication and one comorbidity are eligible. A stratified-cluster randomization design is employed, with 7 hospitals assigned to the control arm and 7 hospitals assigned to the intervention arm. The MALPIP screening tool will be used in the intervention group to review the medications. If PIM is detected, the pharmacists will discuss with doctors and decide whether to stop or reduce the dose. The primary outcomes of this trial are the total number of medications and number of PIM. The secondary outcomes include fall, emergency department visits, readmissions, quality of life and mortality. Outcomes will be measured during enrolment, discharge, 6, 12, and 18 months.
DISCUSSION: This REVMED trial aims to test the hypothesis that a pharmacist-led deprescribing intervention initiated in the hospital will reduce the total number of medications and PIM 18 months after hospital discharge, reducing fall, emergency department visits, readmissions, mortality and lead to improvement in quality of life. Trial findings will quantify the clinical outcomes associated with reducing medications and PIM for hospitalized older adults with polypharmacy.
TRIAL REGISTRATION NUMBER: This trial was prospectively registered at clinicaltrials.gov (NCT05875623) on the 25th of May 2023. NCT05875623 Clinicaltrials.gov URL: NCT05875623 registered on 25th July 2023.
METHOD: This cross-sectional study was conducted in 14 Perak state hospitals and 12 primary health clinics through an online survey. All ward pharmacists and trainee pharmacists with at least 1 month of ward pharmacy experience and working in government-funded health facilities were included. The validated survey tool consisted of demographic characteristics, pharmacists' experience towards challenges (22 items), and their attitude towards adaptive measures (9 items). Each item was measured based on a 5-point Likert scale. One-way ANOVA and logistic regression were employed to determine the association of pharmacists' characteristics against their experience and attitude.
RESULTS: Out of 175 respondents, 144 (81.8%) were female, and 84 (47.7%) were Chinese. Most pharmacists served in the medical ward (124, 70.5%). Commonly reported perceived challenges were difficulties in counselling medication devices (3.63 ± 1.06), difficulties in clerking medication history from family members (3.63 ± 0.99), contacting family members (3.46 ± 0.90), patient's digital illiteracy in virtual counselling (3.43 ± 1.11) and completeness of the electronic records (3.36 ± 0.99). For attitude towards adaptive measures, improving internet connection (4.62 ± 0.58), ensuring availability of multilingual counselling videos (4.45 ± 0.64), and provision of internet-enabled mobile devices (4.39 ± 0.76) were the most agreeable by the pharmacists. Male (AOR: 2.63, CI 1.12-6.16, p = 0.026) and master's degree holders (AOR: 2.79, CI 0.95-8.25, p = 0.063) had greater odds of high perceived challenging experience scores. Master's degree holders (AOR: 8.56, CI 1.741-42.069, p = 0.008) were also more likely to have a positive attitude score towards adaptive measures.
CONCLUSION: Pharmacists faced multiple challenges in the ward pharmacy practice during the COVID-19 pandemic, especially in medication history assessment and patient counselling. Pharmacists, especially those with higher levels of education and longer tenure, exhibited a higher level of agreement towards the adaptive measures. The positive attitudes of pharmacists towards various adaptive measures, such as improvement of internet infrastructure and digital health literacy among patients and family members, warrant immediate action plans from health authorities.
METHOD: Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1's expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients.
RESULT: Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis.
CONCLUSION: Findings from our meta-analysis demonstrated that CYP24A1's expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.
METHODS: A literature review of PubMed with a focus on historical and landmark studies was undertaken to classify the evidence according to the different stages of the IDEAL Framework.
RESULTS: Several different transoral approaches were developed by a small of number of surgeon-innovators on animals and cadavers, and subsequently in first-in-human studies. The trivestibular approach emerged as the safest technique, with further refinements of this technique culminating in TOETVA. The basic steps and indications for this technique have been standardized and it is now being replicated by early adopters in many centres worldwide. The development of TOETVA has closely aligned with the IDEAL Framework, and is currently at stage 2B (Exploration).
CONCLUSION: There is need for multi-institutional collaborations and international registry studies to plan high-quality randomized trials comparing TOETVA with other remote-access approaches and collect long-term follow-up data. In countries where TOETVA has yet to be adopted, the IDEAL Framework will be a useful roadmap for government regulators and professional societies to evaluate, regulate, and provide best practice recommendations for the adoption of this technique.
METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).
RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.
CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.